FDA-approved carbonic anhydrase inhibitors reduce amyloid β pathology and improve cognition, by ameliorating cerebrovascular health and glial fitness.

ABSTRACT:

Introduction

Cerebrovascular pathology is an early and causal hallmark of Alzheimer's disease (AD), in need of effective therapies.

Methods

Based on the success of our previous in vitro studies, we tested for the first time in a model of AD and cerebral amyloid angiopathy (CAA), the carbonic anhydrase inhibitors (CAIs) methazolamide and acetazolamide, Food and Drug Administration-approved against glaucoma and high-altitude sickness.

Results

Both CAIs reduced cerebral, vascular, and glial amyloid beta (Aβ) accumulation and caspase activation, diminished gliosis, and ameliorated cognition in TgSwDI mice. The CAIs also improved microvascular fitness and induced protective glial pro-clearance pathways, resulting in the reduction of Aβ deposition. Notably, we unveiled that

SUBMITTER: Canepa E 

PROVIDER: S-EPMC10600328 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature